This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Obesity is associated with numerous medical conditions, the most devastating of which is diabetes (T2DM). Ove 15 million Americans are afflicted with T2DM which represents the leading cause of end-stage renal disease, blindness, and non-traumatic limb amputation. Recent evidence suggests RYGB to be the most effective treatment available for patients with T2DM. Resolution of T2DM is noted in over 80% of obese patients after RYGB. Post-RYGB improvements in T2DM appear to be the result of changes in gut anatomy which influence intestinal metabolism and endocrine function. Despite this important observation, our current understanding of how changes in gut anatomy improve T2DM is limited. We hypothesize that proteomic analyses of pre- and post-RYGB fasting and post-prandial plasma in patients [unreadable] T2DM will enhance our understanding of how changes in gut anatomy improve T2DM. Based on our established tissue bank containing longitudinal pre- and post-RYGB tissue samples we are in a unique position to collaborate with PNNL and perform these studies. Furthermore, preliminary proteomic analysis of fasting plasma from pre- and post-RYGB patients support this hypothesis and provide proof of concept. The proposed studies have the potential to dramatically influence our understanding of how RYGB improves T2DM and potentially identify new medical therapies. In addition we anticipate they will identify potential mediators for future study, generate preliminary data for future grant submission and scientific data for publication.